This research proposal is a result of the growing awareness that the methods of evaluation in teratology have to be expanded to include biochemical and functional lesions which would go unnoticed with traditional methods of morphologic assessment. The project will examine the effects of prenatal exposure in utero to low levels of organophosphorus insecticides (OP). Such compounds are of ever increasing importance in world agricultural production, and OP residues are known to contaminate soil, food and fiber. Methyl parathion was chosen as the model compound. The emphasis in the selection of doses to be administered orally to pregnant rats from day 6 until the end of gestation is on low levels which are below those that cause overt signs of maternal or embryonal toxicity. Biochemical processes related to nucleic acid and protein synthesis as well as the ontogenesis of the cholinergic system will be investigated in the fetal, neonatal, adolescent and adult nervous system. Radioactive precursors will be used to assess the effects of OP on embryonal metabolic pathways leading to DNA, RNA, lipid, carbohydrate and protein synthesis. All observations will be correlated with a quantitation of the placental transfer and embryonal/fetal concentrations of the OP. An important part of the study are behavioral evaluations of OP exposed offspring in a battery of behavioral tests that extends over a considerable period of the animals lives. These analyses are aimed at the detection of subtle functional lesions, because exposure to a variety of xenobiotics has been recognized as leading to birth defects which often manifest themselves in subtle behavioral changes and only after growth and maturation. At this time the safety evaluation of OP appears far from complete in view of their wide spectrum of potential effects on fundamental processes of cell metabolism and the broadened concerns of teratology.